hnRNPAB Promotes Pancreatic Ductal Adenocarcinoma Extravasation and Liver Metastasis by Stabilizing MYC mRNA

Mol Cancer Res. 2024 Nov 1;22(11):1022-1035. doi: 10.1158/1541-7786.MCR-24-0110.

Abstract

Heterogeneous nuclear ribonucleoprotein AB (hnRNPAB) is considered a cancer-promoting heterogeneous nuclear ribonucleoprotein in many cancers, but its function in pancreatic ductal adenocarcinoma (PDAC) is poorly understood. hnRNPAB was highly expressed in PDAC tissues compared with normal pancreatic tissues, and high expression of hnRNPAB was associated with poor overall survival and recurrence-free survival in patients with PDAC. hnRNPAB promotes migration and invasion of PDAC cells in vitro. In xenograft tumor mouse models, hnRNPAB deprivation significantly attenuated liver metastasis. hnRNPAB mRNA and protein levels are positively associated with MYC in PDAC cells. Mechanistically, hnRNPAB bound to MYC mRNA and prolonged its half-life. hnRNPAB induced PDAC cells to secrete CXCL8 via MYC, which promoted neutrophil recruitment and facilitated tumor cells entrancing into the hepatic parenchyma. These findings point to a novel regulatory mechanism via which hnRNPAB promotes PDAC metastasis. Implications: hnRNPAB participates in the posttranscriptional regulation of the oncogene MYC by binding and stabilizing MYC mRNA, thereby promoting liver metastasis in PDAC.

MeSH terms

  • Animals
  • Carcinoma, Pancreatic Ductal* / genetics
  • Carcinoma, Pancreatic Ductal* / metabolism
  • Carcinoma, Pancreatic Ductal* / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Female
  • Gene Expression Regulation, Neoplastic
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / metabolism
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / pathology
  • Liver Neoplasms* / secondary
  • Male
  • Mice
  • Mice, Nude
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / metabolism
  • Pancreatic Neoplasms* / pathology
  • Proto-Oncogene Proteins c-myc* / genetics
  • Proto-Oncogene Proteins c-myc* / metabolism
  • RNA Stability
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism

Substances

  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • MYC protein, human
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B